디포스핀류 배위자를 함유한 백금(II) 착체의 합성과 항암효과

노영수,노지 마사히데,Noh, Young-Soo,Masahide, Noji 한국약제학회 1990 Journal of Pharmaceutical Investigation Vol.20 No.4

New antitumor-active pt(II) complexes of trans-l-diamine cyclohexane containing diphosphines as a leaving group were synthesized. The structures of the pt(II) complexes were determined by analyzing the infrared and $^{31}P-nuclear$ magnetic resonance spectra. Antitumor activities of the pt(II) complexes were tested against murine leukemia $L_{l210}$ according to the protocol of the National Cancer Institute. All the pt(II) complexes Synthesized were antitumor-active. In particular, water-soluble $[pt(trans-l-dach) (DPPP)](NO_3)_2$ exhibited excellent antitumor activity, giving T/C % values of 341 and 356 respectively, each with four cured mice out of six at a dose of 25 mg/kg. These pt(II) complexes are considered to be worthy of further development.

Isolation and Identification of Antitumor Promoters from the Seeds of Cassia tora

( Yeung Beom Park ),( Seon Bong Kim ) 한국미생물 · 생명공학회 2011 Journal of microbiology and biotechnology Vol.21 No.10

A methanol extract of Cassia tora seeds was successively partitioned with diethyl ether, chloroform, ethyl acetate, and water, and the antitumor-promoting activity of the solvent fractions was determined by inhibition of Epstein- Barr virus early antigen (EBV-EA) activation induced by teleocidin B-4 in Raji cells. The diethyl ether (68.7%) and chloroform (91.2%) fractions and the hydrolysate (94.3%) of the ethyl acetate fraction had strong inhibitory activities. The chloroform and ethyl acetate fractions were chromatographed on silica gel and further purified by HPLC. Three active compounds, obtusifolin-2-glucoside (75.0%), chryso-obtusin-6-glucoside (56.8%), and norrubrofusarin- 6-glucoside (39.4%), were obtained from the ethyl acetate fraction, and two active compounds, questin (97.9%) and chryso-obtusin (53.8%), were isolated from the chloroform fraction.

Phellinus gilvus의 항암활성, 간보호 및 항돌연변이성에 대한 평가

강은희,김길수,박승춘,Kang, Eun-Hee,Kim, Kil-Soo,Park, Seung-Chun 대한수의학회 2008 大韓獸醫學會誌 Vol.48 No.1

This study was carried out to evaluate the antitumor, hepatoprotective and antimutagenic activities on hot water extract of Phellinus gilvus (PGE). Growth of tumor in mice that were orally given $0.25,0.5,1.0,2.0g\;kg^{-1}$ dose of PGE was inhibited in a dose-dependent manner (p < 0.05). The hepatoprotective effect of PGE in the carbon tetrachloride ($CCl_4$)-intoxicated rats was studied. In $CCl_4$ + PGE group, PGE was orally administered with 100 mg/kg/day dose 7 days before the treatment of $CCl_4$. The serum activity of aspartate aminotransferase and alanine aminotransferase in $CCl_4$ + PGE group were decreased at a rate of 59.6% and 54.1% compared with those in $CCl_4$ group, respectively (p < 0.05). Also, total cholesterol and triglyceride in $CCl_4$ + PGE group were significantly decreased at a rate of 90% and 73.6% compared with those in $CCl_4$ group (p < 0.05). In the Ames test, we confirmed PGE doesn't have any activity as a mutant, and PGE showed inhibitory effect against mutagenesis induced by 2-amino fluride and sodium azide in Salmonella typhimurium TA98, TA100 and TA1535 in a dose-dependent manner. From the above results, we may suggest that PGE might have useful as a material for functional food and/or animal pharmaceutics.

시호 추출물이 면역계 세포의 활성에 미치는 영향

조정곤,김종면,Cho, Jeong-gon,Kim, Jong-myeon 대한수의학회 1994 大韓獸醫學會誌 Vol.34 No.4

The root of Bupleurum falcatum L.(BF) has been widely used in oriental medicine as a major camponent in many prescriptions for chronic hepatitis, renal disease, tuberculosis and some other infectious diseases. Many attempts have done to investigate the therapeutic effects of these principles. However, any kinds of screenig on immune regulatory- and antitumor- effects of BF has not been reported. The present study, therefore, was undertaken to investigate the BF-effects on cellular- and humoral-immune responses, phagocytic activities of macrophages, lymphokine- and Immunoglobulin(Ig)-production of lymphocytes, tumorigenesis of implanted sarcoma 180 cells and B16 melanoma cells, and proliferations of some tumor cell lines(Fsa II, 3LL and EL4). BF increased phagocytic activities of mouse peritoneal macrophages in a dose- and time-dependent fashion. Arthus reaction and antibody responses to SRBC were slightly enhanced but delayed hypersensitivity was depresed when BF was injected before- and after-SRBC sensitization. BF inhibited the proliferative responses of human tonsillar lymphocytes to PHA- and Con A-stimulation but slightly augmented the response of these cells to Staphylococcus aureus Cowan 1(SAC)-activation. Ig secretion of human mononuclear cells activated with SAC was slightly increased by BF. BF significantly augmented the SAC-induced IL 6 production of human mononuclear cells but not influenced Con Ainduced IL 2 secretion. NK cell activities of mouse splenocytes were somewhat increased when BF was pretreated and this responses were due to the increment of binding affinities of effector cells to target cells and of lytic activities of effector cells against target cells. In vitro BF significantly inhibited the proliferations of cancer cells such as Fsa II, 3LL and EL4 strains. BF decreased not only the frequency of tumor induction but also the tumor size per sarcoma 180 or B16 cell-implanted mouse. Taken together, these results indicate that BF is one of the potential immunomodulator, and suggest its possibility to be used as a desirable antitumor agent.

Streptomyces sp. YBE-316이 생산하는 항암성 항생물질의 정제 및 특성

박재홍,함병권,배동훈,유주현 한국산업미생물학회 1995 한국미생물·생명공학회지 Vol.23 No.3

미생물로부터의 새로운 항암성 항생물질 개발을 목적으로 토양으로부터 분리한 Streptomyces sp. YBE316이 생산하는 항암성 항생물질은 오직 균체 내에만 존재하였고 pH 5.0∼10.0까지 안정하였으며 중성에서 활성이 가장 높았고 열에 대한 안전성은 낮았다 본 항암성 항생물질의 유기용매에 대한 용해도와 안정성을 검토한 결과 methanol에서 가장 좋았으며, 정제는 균체로부터 acetone 추출, butanol 추출, silica gel column chromatography 등을 이용하여 순차적으로 행하였다. 본 물질의 항암활성은 낮았으며, 항균활성은 항세균보다는 항진균 활성이 강하였다. 본 항암성 항생물질은, 기초적인 기기분석을 행한 결과, polyene계의 pentaene계 항생물질중 eurocidin이나 capacidin type의물질로 추측되었으며, 그 분자량은 최소한 683.0 dalton 이상이었고, mycosamine이나 perosamine 등의 amino sugar가 아닌 당으로 glycosylation 되어 있는 것으로 추측되었다. For the development of new antitumor antibiotics produced by microorganisms, Streptomyces sp. YBE-316 was isolated from soil. The productivity of the antitumor antibiotic from Streptomyces sp. YBE-316 gradually increased after 60 hours, and was maximum after 100 hours after inoculation in growth medium (2.0% sucrose, 1.0% soybean meal, 0.1% K_2HPO_4, pH 7.0) at 30℃, 150 rpm, 5 NL/min by 30 ℓ jar fermentor. This antitumor antibiotic was present only in mycelium, and stable in pH 5.0∼10.0 for 20 minutes at 100℃. Antitumor and antibiotic activities were maintained at neutral pH, and heat stability was low. This antitumor antibiotic was soluble in methanol and ethanol, and insoluble in water, ethyl acetate, chloroform, and n-hexane. This antitumor antibiotic was sequentially purified by acetone extraction from mycelium, butanol extraction, and silica gel column chromatography. Antitumor activity was low against most tested cell lines, but antibiotic activity was high and low against yeasts and bacteria, respectively. The visualization test showed that this antitumor antibiotic had higher hydroxyl, ketone, amino, carboxyl groups, and sugar(s) in its structure. Instrumental analyses showed that this antitumor antibiotic was a pentaene in polyene class antibiotics. In pentaene class antibiotics, this was considered as an eurocidin or capacidin type antibiotics. The molecular weight of this antitumor antibiotic was higher than 683.0 daltons, and this antitumor antibiotic might be glycosylated by other sugar(s), instead of mycosamine or perosamine, an amino sugar.

韓醫學의 抗腫瘍 免疫治療에 관한 연구 : 1990年 以後 發표된 實驗論文을 中心으로

강연이,김태임,박종오,김성훈,박종대,김동희 대한동의생리학회,대한동의병리학회 2003 동의생리병리학회지 Vol.17 No.1

This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were classified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer center. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-actibvation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by an antitumor experiments, cytotoxic effect was 48.1%, survival time was 48.1%, and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate to the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immnunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to connect between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (OOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

Ginsengenin derivatives synthesized from 20(R)-panaxotriol: Synthesis, characterization, and antitumor activity targeting HIF-1 pathway

Guo, Hong-Yan,Xing, Yue,Sun, Yu-Qiao,Liu, Can,Xu, Qian,Shang, Fan-Fan,Zhang, Run-Hui,Jin, Xue-Jun,Chen, Fener,Lee, Jung Joon,Kang, Dongzhou,Shen, Qing-Kun,Quan, Zhe-Shan The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.6

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by ¹H-NMR, ¹³C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC₅₀ < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC₅₀ > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

한국산 생약으로부터 항암물질의 개발(제6보). -금은화 Ethyl Acetate 가용성 분획의 인체 구강유상피암종세포에 미치는 세포독성작용-

한두석,백경현,김영옥,최규은,곽정숙,백승화,Han, Du-Seok,Baek, Kyong-Hyun,Kim, Young-Ok,Choi, Kyu-Eun,Kwag, Jung-Suk,Baek, Seung-Hwa 한국생약학회 1998 생약학회지 Vol.29 No.1

This study was carried out to develop antitumor agents based on effects of the ethyl acetate soluble fraction of the methanolic extract of Lonicerae flos on human oral epitheloid carcinoma cells. Human oral epitheloid carcinoma cells were cultured in RPMI-1640 media containing 10% fetal bovine serum, antibiotic, and fungizone. After incubation for 24 hrs, the cells were treated with A, B, C, D, and E fractions for 48hrs under the same condition. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazoliumbromide), NR (Neutral red) and SRB (Sulforhodamine B protein) assay were performed. The light microscopic findings were observed by inverted microscope. In MTT assay, fraction B was shown significant antitumor activity (P<0.001), fraction E was shown significant antitumor activities (P<0.05), but the other fractions were not shown. In NR assay, fraction B was shown significant antitumor activity (P<0.001). In SRB assay, fractions B was shown significant antitumor activities (P<0.01). fractions A and D were shown significant antitumor activities (P<0.05). but the other fractions were not shown. In light microscopy. the fraction B of the ethyl acetate soluble fraction of the methanolic extract of Lonicerae flos showed the highest antitumor activity. These finding suggested that fraction B possessed the most antitumorous agent.

분심기음의 항암작용 및 면역기능에 관한 연구

여대원,김진성,윤상협,류봉하,류기원 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

This study was performed to investigate the effect of Bunsimgieum on antitumor effect after sarcoma-180 cells transplantation into peritoneal cavity or left groin and immune responses on the depressed immunity induced by methotrexate in mice. The Bunsimgieum extract of 10㎎/㎏ was orally administered 14 days for antitumor effects and 21 days for immune responses. 50% inhibitory concentration(IC_(50)) of SUN-1, SUN-C4. and SUN-396 cancer cell, mean sunvival days and body weight of tumor bearing mice, and growth of tumor mass for antitumor effect; delayed type hypersentivity, hemagglutinin titer, hemolysis titer, rosette forming cells, natured killer cell activity, lymphocyte transformation. productivity of interleukin-2 and phagocytic activity for their immune responses were measured in ICR mice. Significance in antitumor effect is noted in the enlongation of mean life days and inhibition of tumor growth(p<0.01 respectively). Significance of immune responses is also noted in hemolysis titer, lymphocyte transfumotion IL-2 productivity, phagocytic activity, and natural killer cell activity at E/T ratio 100 : 1(p<0.01, respectively). Significant in rosette cell formation was seen dosage of 20㎎/㎏(p<0.01) However, Difference of body weight as antitumor effect, delayed type hypersensitivity, and hemagglutinin titer were not shown significantly. According to the above results, it could be suggested that Bunsimgieum has prominent antitumor and immunity enhancing effect.

분심기음의 항암작용 및 면역기능에 관한 연구

김진성,윤상협,류봉하,류기원,여대원,Kim Jin-Sung,Yoon Sang-Hyub,Ryu Bong-Ha,Ryu Ki-Won,Yeo Dae-Won 대한한방내과학회 2003 大韓韓方內科學會誌 Vol.24 No.2

This study was performed to investigate the effect of Bunsimgieum on antitumor effect after sarcoma-180 cells transplantation into peritoneal cavity or left groin and immune responses on the depressed immunity induced by methotrexate in mice. The Bunsimgieum extract of 10mg/kg was orally administered 14 days for antitumor effects and 21 days for immune responses. 50% inhibitory concentration($IC_{50}$) of SUN-1, SUN-C4, and SUN-396 cancer cell, mean sunvival days and body weight of tumor bearing mice, and growth of tumor mass for antitumor effect; delayed type hypersentivity, hemagglutinin titer, hemolysis titer, rosette forming cells, natured killer cell activity, lymphocyte transformation, productivity of interleukin-2, and phagocytic activity for their immune responses were measured in ICR mice. Significance in antitumor effect is noted in the enlongation of mean life days and inhibition of tumor growth(p<0.01, respectively). Significance of immune responses is also noted in hemolysis titer, lymphocyte transfumotion, IL-2 productivity, phagocytic activity, and natural killer cell activity at E/T ratio 100:1(p<0.01, respectively). Significant in rosette cell formation was seen at dosage of 20mg/kg(p<0.01). However, Difference of body weight as antitumor effect, delayed type hypersensitivity, and hemagglutinin titer were not shown significantly. According to the above results, it could be suggested that Bunsimgieum has prominent antitumor and immunity enhancing effect.